tbuckley/cabot-search huggingface dataset:
Internal models of self-motion: neural computations by the vestibular cerebellum
Authors: Kathleen E. Cullen
Journal: Trends in Neurosciences (2023)

The vestibular cerebellum plays an essential role in maintaining our balance and ensuring perceptual stability during activities of daily living. Here I examine three key regions of the vestibular cerebellum: the floccular lobe, anterior vermis (lobules I–V), and nodulus and ventral uvula (lobules X–IX of the posterior vermis). These cerebellar regions encode vestibular information and combine it with extravestibular signals to create internal models of eye, head, and body movements, as well as their spatial orientation with respect to gravity. To account for changes in the external environment and/or biomechanics during self-motion, the neural mechanisms underlying these computations are continually updated to ensure accurate motor behavior. To date, studies on the vestibular cerebellum have predominately focused on passive vestibular stimulation, whereas in actuality most stimulation is the result of voluntary movement. Accordingly, I also consider recent research exploring these computations during active self-motion and emerging evidence establishing the cerebellum's role in building predictive models of self-generated movement.
Integrated study of systemic and local airway transcriptomes in asthma reveals causal mediation of systemic effects by airway key drivers
Authors: Lingdi Zhang, Yoojin Chun, Haritz Irizar, Zoe Arditi, Galina Grishina, Alexander Grishin, Alfin Vicencio, Supinda Bunyavanich
Journal: Genome Medicine (2023)

Abstract Background Systemic and local profiles have each been associated with asthma, but parsing causal relationships between system-wide and airway-specific processes can be challenging. We sought to investigate systemic and airway processes in asthma and their causal relationships. Methods Three hundred forty-one participants with persistent asthma and non-asthmatic controls were recruited and underwent peripheral blood mononuclear cell (PBMC) collection and nasal brushing. Transcriptome-wide RNA sequencing of the PBMC and nasal samples and a series of analyses were then performed using a discovery and independent test set approach at each step to ensure rigor. Analytic steps included differential expression analyses, coexpression and probabilistic causal (Bayesian) network constructions, key driver analyses, and causal mediation models. Results Among the 341 participants, the median age was 13 years (IQR = 10–16), 164 (48%) were female, and 200 (58.7%) had persistent asthma with mean Asthma Control Test (ACT) score 16.6 (SD = 4.2). PBMC genes associated with asthma were enriched in co-expression modules for NK cell-mediated cytotoxicity (fold enrichment = 4.5, FDR = 6.47 × 10 −32 ) and interleukin production (fold enrichment = 2.0, FDR = 1.01 × 10 −15 ). Probabilistic causal network and key driver analyses identified NK cell granule protein ( NKG7 , fold change = 22.7, FDR = 1.02 × 10 −31 ) and perforin ( PRF1 , fold change = 14.9, FDR = 1.31 × 10 −22 ) as key drivers predicted to causally regulate PBMC asthma modules. Nasal genes associated with asthma were enriched in the tricarboxylic acid (TCA) cycle module (fold enrichment = 7.5 FDR = 5.09 × 10 −107 ), with network analyses identifying G3BP stress granule assembly factor 1 ( G3BP1 , fold change = 9.1 FDR = 2.77 × 10 −5 ) and InaD-like protein ( INADL , fold change = 5.3 FDR = 2.98 × 10 −9 ) as nasal key drivers. Causal mediation analyses revealed that associations between PBMC key drivers and asthma are causally mediated by nasal key drivers (FDR = 0.0076 to 0.015). Conclusions Integrated study of the systemic and airway transcriptomes in a well-phenotyped asthma cohort identified causal key drivers of asthma among PBMC and nasal transcripts. Associations between PBMC key drivers and asthma are causally mediated by nasal key drivers.
A potential novel therapy addressing RNA oxidative damage in AKI
Authors: Cheng Wan, Chun Zhang
Journal: Molecular Therapy (2023)

Oxidative stress plays a vital role in the pathogenesis of various diseases, as excessive free radicals can damage cellular components including nucleic acid, lipid, and protein, resulting in progressive physiological dysfunction. Compared with DNA, lipid, and protein, RNA is indicated to be more vulnerable to oxidative damage. 1 Kong Q. Lin C.L.G. Oxidative damage to RNA: mechanisms, consequences, and diseases. Cell. Mol. Life Sci. 2010; 67: 1817-1829 Crossref PubMed Scopus (266) Google Scholar However, RNA oxidation has drawn little attention, and even today, the damage mechanism remains obscure, thus making this an area with great potential for exploration. Targeting RNA oxidation by ISG20-mediated degradation is a potential therapeutic strategy for acute kidney injuryJia et al.Molecular TherapyJuly 13, 2023In BriefYi and colleagues provide direct evidence that RNA oxidation actually contributes to the pathogenesis of AKI and ISG20 protects against AKI through mediating the degradation of oxidized RNA, thereby preventing the activation of ER stress and UPR cascades. Targeting ISG20-handled RNA oxidation may be an innovative therapeutic strategy for AKI. Full-Text PDF Open Access
Dosage compensation of Z sex chromosome genes in avian fibroblast cells
Authors: Ruslan Deviatiiarov, Hiroki Nagai, Galym Ismagulov, Anastasia Stupina, Kazuhiro Wada, Shinji Ide, Noriyuki Toji, Heng Zhang, Woranop Sukparangsi, Sittipon Intarapat, Oleg Gusev, Guojun Sheng
Journal: Genome biology (2023)

Abstract In birds, sex is genetically determined; however, the molecular mechanism is not well-understood. The avian Z sex chromosome (chrZ) lacks whole chromosome inactivation, in contrast to the mammalian chrX. To investigate chrZ dosage compensation and its role in sex specification, we use a highly quantitative method and analyze transcriptional activities of male and female fibroblast cells from seven bird species. Our data indicate that three fourths of chrZ genes are strictly compensated across Aves, similar to mammalian chrX. We also present a complete list of non-compensated chrZ genes and identify Ribosomal Protein S6 (RPS6) as a conserved sex-dimorphic gene in birds.
DISCERN: deep single-cell expression reconstruction for improved cell clustering and cell subtype and state detection
Authors: Fabian Hausmann, Can Ergen, Robin Khatri, Mohamed Marouf, Sonja Hänzelmann, Nicola Gagliani, Samuel Huber, Pierre Machart, Stefan Bonn
Journal: Genome biology (2023)

Single-cell sequencing provides detailed insights into biological processes including cell differentiation and identity. While providing deep cell-specific information, the method suffers from technical constraints, most notably a limited number of expressed genes per cell, which leads to suboptimal clustering and cell type identification.Here, we present DISCERN, a novel deep generative network that precisely reconstructs missing single-cell gene expression using a reference dataset. DISCERN outperforms competing algorithms in expression inference resulting in greatly improved cell clustering, cell type and activity detection, and insights into the cellular regulation of disease. We show that DISCERN is robust against differences between batches and is able to keep biological differences between batches, which is a common problem for imputation and batch correction algorithms. We use DISCERN to detect two unseen COVID-19-associated T cell types, cytotoxic CD4+ and CD8+ Tc2 T helper cells, with a potential role in adverse disease outcome. We utilize T cell fraction information of patient blood to classify mild or severe COVID-19 with an AUROC of 80% that can serve as a biomarker of disease stage. DISCERN can be easily integrated into existing single-cell sequencing workflow.Thus, DISCERN is a flexible tool for reconstructing missing single-cell gene expression using a reference dataset and can easily be applied to a variety of data sets yielding novel insights, e.g., into disease mechanisms.
Intussusception as a complication of idiopathic nephrotic syndrome
Authors: Fanny Dreant, Benedicte Sautenet, Christelle Barbet, Jean-Michel Halimi
Journal: Kidney International (2023)

A 19-year-old male patient presented with abdominal pain associated with a relapse of minimal change disease (serum creatinine: 90 μmol/l; albumin: 1.6 g/dl; proteinuria: 7.8 g/g). A right iliac fossa ileo–ileal intussusception was found on the computed tomography (CT) scan (Figure 1). The pain subsided with administration of paracetamol but recurred 2 days later. A second CT scan showed 2 other right lumbar jejuno–jejunal intussusceptions, and 1 upper-left-quadrant ileo–ileal intussusception, but the right iliac fossa ileo–ileal intussusception was no longer visible (Figure 2).
Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges
Authors: Longhong Zhu, Shihua Li, Xiao-Jiang Li, Peng Yin
Journal: Translational Neurodegeneration (2023)

Abstract In order to dissect amyotrophic lateral sclerosis (ALS), a multigenic, multifactorial, and progressive neurodegenerative disease with heterogeneous clinical presentations, researchers have generated numerous animal models to mimic the genetic defects. Concurrent and comparative analysis of these various models allows identification of the causes and mechanisms of ALS in order to finally obtain effective therapeutics. However, most genetically modified rodent models lack overt pathological features, imposing challenges and limitations in utilizing them to rigorously test the potential mechanisms. Recent studies using large animals, including pigs and non-human primates, have uncovered important events that resemble neurodegeneration in patients’ brains but could not be produced in small animals. Here we describe common features as well as discrepancies among these models, highlighting new insights from these models. Furthermore, we will discuss how to make rodent models more capable of recapitulating important pathological features based on the important pathogenic insights from large animal models.
Correction: Circ-HuR suppresses HuR expression and gastric cancer progression by inhibiting CNBP transactivation
Authors: Feng Yang, Anpei Hu, Dan Li, Jianqun Wang, Yanhua Guo, Yang Liu, Hongjun Li, Yajun Chen, Xiaojing Wang, Kai Huang, Liduan Zheng, Qiangsong Tong
Journal: Molecular Cancer (2023)
Mental health among children and adolescents after SARS-CoV-2 infection: A prospective study in a tertiary university hospital
Authors: Olivia Mari Matsuo, Livia Lindoso, Heloisa Helena de Sousa Marques, Guilherme V. Polanczyk, Sylvia Costa Lima Farhat, Vera Bain, Thais T. Fink, Fernanda Martins, Camilla Astley, Priscila Suguita, Vitor Trindade, Simone Correa-Silva, Patricia Palmeira, Camila Sanson Yoshino de Paula, Nadia Litvinov, Juliana Caires O.A. Ferreira, Neusa Keico Sakita, Bruno Gualano, Clovis Artur A. Silva, Maria Fernanda Badue Pereira
Journal: Journal of Infection (2023)
Patient Perspectives on Living With Severe Prurigo Nodularis
Authors: Danielle Rodriguez, Shawn G. Kwatra, Carla Dias-Barbosa, Fanyang Zeng, Zarif K. Jabbar Lopez, Christophe Piketty, Jorge Puelles
Journal: JAMA Dermatology (2023)

Because of a paucity of qualitative research on prurigo nodularis (PN), the symptoms and impacts of PN that are most important to patients are poorly understood.
Deep Learning for Cardiovascular Imaging
Authors: Ramsey M. Wehbe, Aggelos K. Katsaggelos, Kristian J. Hammond, Ha Hong, Faraz S. Ahmad, David Ouyang, Sanjiv J. Shah, Patrick M. McCarthy, James D. Thomas
Journal: JAMA Cardiology (2023)

Artificial intelligence (AI), driven by advances in deep learning (DL), has the potential to reshape the field of cardiovascular imaging (CVI). While DL for CVI is still in its infancy, research is accelerating to aid in the acquisition, processing, and/or interpretation of CVI across various modalities, with several commercial products already in clinical use. It is imperative that cardiovascular imagers are familiar with DL systems, including a basic understanding of how they work, their relative strengths compared with other automated systems, and possible pitfalls in their implementation. The goal of this article is to review the methodology and application of DL to CVI in a simple, digestible fashion toward demystifying this emerging technology.At its core, DL is simply the application of a series of tunable mathematical operations that translate input data into a desired output. Based on artificial neural networks that are inspired by the human nervous system, there are several types of DL architectures suited to different tasks; convolutional neural networks are particularly adept at extracting valuable information from CVI data. We survey some of the notable applications of DL to tasks across the spectrum of CVI modalities. We also discuss challenges in the development and implementation of DL systems, including avoiding overfitting, preventing systematic bias, improving explainability, and fostering a human-machine partnership. Finally, we conclude with a vision of the future of DL for CVI.Deep learning has the potential to meaningfully affect the field of CVI. Rather than a threat, DL could be seen as a partner to cardiovascular imagers in reducing technical burden and improving efficiency and quality of care. High-quality prospective evidence is still needed to demonstrate how the benefits of DL CVI systems may outweigh the risks.
Abortions in States Without Bans Surge Post-<i>Roe</i>
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Treatment of Hydroxyurea-Induced Ulcers With Timolol
Authors: Angelina S. Hwang, Elika Hoss, Mark R. Pittelkow, Yul W. Yang
Journal: JAMA Dermatology (2023)

This report evaluates the use of timolol in 2 patients with long-term hydroxyurea use and lower-extremity ulcers resistant to other treatments.
New Technology and Bile Duct Injuries
Authors: Liane S. Feldman, L. Michael Brunt
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Polypharmacy and Deprescribing in Older Adults
Authors: Wade Thompson, Emily G. McDonald
Journal: Annual Review of Medicine (2023)

Older adults commonly end up on many medications. Deprescribing is an important part of individualizing care for older adults. It is an opportunity to discuss treatment options and revisit medications that may not have been reassessed in many years. A large evidence base exists in the field, suggesting that deprescribing is feasible and safe, though questions remain about the potential clinical benefits. Deprescribing research faces a myriad of challenges, such as identifying and employing the optimal outcome measures. Further, there is uncertainty about which deprescribing approaches are likely to be most effective and in what contexts. Evidence on barriers and facilitators to deprescribing has underscored how deprescribing in routine clinical practice can be complex and challenging. Thus, finding practical, sustainable ways to implement deprescribing is a priority for future research in the field.
Network-Based Spreading of Gray Matter Changes Across Different Stages of Psychosis
Authors: Sidhant Chopra, Ashlea Segal, Stuart Oldham, Alexander Holmes, Kristina Sabaroedin, Edwina R. Orchard, Shona M. Francey, Brian O’Donoghue, Vanessa Cropley, Barnaby Nelson, Jessica Graham, Lara Baldwin, Jeggan Tiego, Hok Pan Yuen, Kelly Allott, Mario Alvarez-Jimenez, Susy Harrigan, Ben D. Fulcher, Kevin Aquino, Christos Pantelis, Stephen J. Wood, Mark Bellgrove, Patrick D. McGorry, Alex Fornito
Journal: JAMA Psychiatry (2023)

Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown.
Prenatal Exposure to Nonpersistent Environmental Chemicals and Postpartum Depression
Authors: Melanie H. Jacobson, Ghassan B. Hamra, Catherine Monk, Rosa M. Crum, Sudhindra Upadhyaya, Lyndsay A. Avalos, Theresa M. Bastain, Emily S. Barrett, Nicole R. Bush, Anne L. Dunlop, Assiamira Ferrara, Morgan R. Firestein, Alison E. Hipwell, Kurunthachalam Kannan, Johnnye Lewis, John D. Meeker, Douglas M. Ruden, Anne P. Starling, Deborah J. Watkins, Qi Zhao, Leonardo Trasande, P B Smith, K L Newby, Lisa P Jacobson, C B Parker, Richard C Gershon, David Cella, Catherine Karr, Alex Mason, Frances Tylavsky, Jean Kerver, Charles J Barone, Nigel Paneth, Akram N Alshawabkeh, Sheela Sathyanarayana, Dana Dabelea, Jose Cordero, Kaja Z LeWinn, Chris Fussman
Journal: JAMA Psychiatry (2023)

Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored.
Safety and Efficacy of Sustained Automated Insulin Delivery Compared With Sensor and Pump Therapy in Adults With Type 1 Diabetes at High Risk for Hypoglycemia: A Randomized Controlled Trial
Authors: Eric Renard, Michael Joubert, Orianne Villard, Bleuenn Dreves, Yves Reznik, Anne Farret, Jerome Place, Marc D. Breton, Boris P. Kovatchev
Journal: Diabetes Care (2023)

OBJECTIVE Assess the safety and efficacy of automated insulin delivery (AID) in adults with type 1 diabetes (T1D) at high risk for hypoglycemia. RESEARCH DESIGN AND METHODS Participants were 72 adults with T1D who used an insulin pump with Clarke Hypoglycemia Perception Awareness scale score &amp;gt;3 and/or had severe hypoglycemia during the previous 6 months confirmed by time below range (TBR; defined as sensor glucose [SG] reading &amp;lt;70 mg/dL) of at least 5% during 2 weeks of blinded continuous glucose monitoring (CGM). Parallel-arm, randomized trial (2:1) of AID (Tandem t:slim ×2 with Control-IQ technology) versus CGM and pump therapy for 12 weeks. The primary outcome was TBR change from baseline. Secondary outcomes included time in target range (TIR; 70–180 mg/dL), time above range (TAR), mean SG reading, and time with glucose level &amp;lt;54 mg/dL. An optional 12-week extension with AID was offered to all participants. RESULTS Compared with the sensor and pump (S&amp;P), AID resulted in significant reduction of TBR by −3.7% (95% CI −4.8, −2.6), P &amp;lt; 0.001; an 8.6% increase in TIR (95% CI 5.2, 12.1), P &amp;lt; 0.001; and a −5.3% decrease in TAR (95% CI −87.7, −1.8), P = 0.004. Mean SG reading remained similar in the AID and S&amp;P groups. During the 12-week extension, the effects of AID were sustained in the AID group and reproduced in the S&amp;P group. Two severe hypoglycemic episodes occurred using AID. CONCLUSIONS In adults with T1D at high risk for hypoglycemia, AID reduced the risk for hypoglycemia more than twofold, as quantified by TBR, while improving TIR and reducing hyperglycemia. Hence, AID is strongly recommended for this specific population.
New Biological Therapies for Multiple Myeloma
Authors: Alfred L. Garfall
Journal: Annual Review of Medicine (2023)

Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable suite of new therapies developed over the last 25 years has enabled durable disease control in most patients. This article briefly introduces the clinical features of multiple myeloma and aspects of multiple myeloma biology that modern therapies exploit. Key current and emerging treatment modalities are then reviewed, including cereblon-modulating agents, proteasome inhibitors, monoclonal antibodies, other molecularly targeted therapies (selinexor, venetoclax), chimeric antigen receptor T cells, T cell–engaging bispecific antibodies, and antibody–drug conjugates. For each modality, mechanism of action and clinical considerations are discussed. These therapies are combined and sequenced in modern treatment pathways, discussed at the conclusion of the article, which have led to substantial improvements in outcomes for multiple myeloma patients in recent years.